Several recent studies have investigated the phenomenon of acute opioid physical dependence or antagonist sensivitity in humans. These studies have shown that a mild withdrawal syndrome can be precipitated by the opioid antagonist, naloxone, administered 45 minutes to 24 hours after a single dose of morphine. These findings are particularly interesting given that the opioid abstinence syndrome has traditionally been thought to develop only after prolonged exposure to opiates. However, these studies have only used non-dependent opiate-experienced subjects. It is not known whether or to what extent an opiate history contributes to the development of acute dependence. If differences in agonist and/or antagonist sensitivity are found between opiate-experienced and opiate-naive individuals, it could reflect residual tolerance or dependence in opiate-experienced individuals due to their chronic opioid exposure. Another interesting possibility is that differences in sensitivity may reflect biological differences between opiate-experienced and opiate-naive individuals that predate initial drug use and thus confer some vulnerability or predisposition to use or abuse opiate drugs. This research will examine the following issues: a) differences in subjective and physiological sensitivity to opioid agonists between opioid-experienced and opioid naive subjects, b) differences in acute antagonist-precipitated withdrawal (antagonist sensitivity) between these groups, and c) whether any differences in antagonist sensitivity are related to dose of the antagonist. Subject testing was begun in 1990 and is nearly completed. A preliminary report of data will be presented at the 1991 meeting of the Committee on Problems of Drug Dependence.